Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

{ 'indexed': {'date-parts': [[2022, 5, 30]], 'date-time': '2022-05-30T04:42:53Z', 'timestamp': 1653885773518}, 'reference-count': 44, 'publisher': 'MDPI AG', 'issue': '6', 'license': [ { 'start': { 'date-parts': [[2022, 5, 28]], 'date-time': '2022-05-28T00:00:00Z', 'timestamp': 1653696000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in ' 'mechanically ventilated patients with the coronavirus disease (COVID-19) has not been ' 'well-defined. This randomized controlled trial included 175 eligible adult patients with ' 'COVID-19 who were treated with mechanical ventilation at the University Hospital of Split ' 'between October 2020 and June 2021. Patients were randomized and allocated to a control group ' '(no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% ' 'saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, ' 'while secondary outcomes included all-cause mortality. Routine inhalation therapy had no ' 'effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p &gt; 0.05). ' 'Secondary analyses revealed a significant reduction of Gram-positive and ' 'methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, ' 'the bicarbonate group had a statistically significantly lower incidence of Gram-positive ' 'bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group ' '(19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower ' 'incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group ' '(7.7%), 5% saline group (14.3%), and control group (34.6%; p &lt; 0.001). Longer duration of ' 'ventilator therapy was the only significant, independent predictor of any bacterial or fungal ' 'VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI ' '1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the ' 'overall VAP incidence or all-cause mortality. Further studies should explore the secondary ' 'findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated ' 'patients.</jats:p>', 'DOI': '10.3390/microorganisms10061118', 'type': 'journal-article', 'created': {'date-parts': [[2022, 5, 30]], 'date-time': '2022-05-30T03:43:03Z', 'timestamp': 1653882183000}, 'page': '1118', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated ' 'COVID-19 Patients: A Randomized Controlled Trial', 'prefix': '10.3390', 'volume': '10', 'author': [ {'given': 'Nikola', 'family': 'Delić', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-9272-6906', 'authenticated-orcid': False, 'given': 'Andrija', 'family': 'Matetic', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-7003-8192', 'authenticated-orcid': False, 'given': 'Josipa', 'family': 'Domjanović', 'sequence': 'additional', 'affiliation': []}, {'given': 'Toni', 'family': 'Kljaković-Gašpić', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5621-580X', 'authenticated-orcid': False, 'given': 'Lenko', 'family': 'Šarić', 'sequence': 'additional', 'affiliation': []}, {'given': 'Darko', 'family': 'Ilić', 'sequence': 'additional', 'affiliation': []}, {'given': 'Svjetlana', 'family': 'Došenović', 'sequence': 'additional', 'affiliation': []}, {'given': 'Josipa', 'family': 'Domazet', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ruben', 'family': 'Kovač', 'sequence': 'additional', 'affiliation': []}, {'given': 'Frane', 'family': 'Runjić', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sanda Stojanović', 'family': 'Stipić', 'sequence': 'additional', 'affiliation': []}, {'given': 'Božidar', 'family': 'Duplančić', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2022, 5, 28]]}, 'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jama.2020.2648'}, {'key': 'ref2'}, {'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/antibiotics10050545'}, {'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/CCM.0b013e3182281f33'}, {'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1097/MCC.0000000000000908'}, {'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.1080/17476348.2017.1359090'}, {'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s40261-019-00861-x'}, { 'key': 'ref8', 'first-page': '309', 'article-title': 'Evaluation of the Effect of Nebulized N-Acetylcysteine on Respiratory ' 'Secretions in Mechanically Ventilated Patients: Randomized Clinical ' 'Trial', 'volume': '40', 'author': 'Masoompour', 'year': '2015', 'journal-title': 'Iran. 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